2.1 Kidney Cancer
Kidney cancer is the second most common malignant tumor (after bladder cancer) of the urinary system (including the genital tract) in males. According to a report released by the National Institute of Cancer in 1995, an estimated 28,000 new cases are diagnosed annually, representing 3% of all new cancers found in adults, with an annual death of about 12,000. Most renal cell carcinomas occur in only one kidney, although 2% to 4% of patients have tumors in both kidneys. Kidney cancer is more common among urban residents and is most commonly diagnosed at age 50 to 70. It occurs in men twice as frequently as it does in women. Certain geographical areas throughout the world have a higher incidence, such as the United States and Scandinavia. In the United States, black men have a slightly higher risk than Caucasian men.
Although the exact cause of renal cell carcinoma is not known, several risk factors have been implicated in its development. The greatest risk factor is tobacco use. Obesity and hypertension (high blood pressure) have also been associated with kidney cancer, although to a lesser degree. Specific genetic factors increase the risk of developing renal cell carcinoma, such as Von Hippel-Lindau disease and other rare familial or hereditary diseases that involve genetic abnormalities. Other risk factors include exposure to asbestos, coke oven workers, long-term dialysis, phenacetin use, and bladder cancer.
Detecting renal cell carcinoma in its early stages is difficult because symptoms typically do not occur until the tumor has grown fairly large and displaces other nearby organs. In the latter stages, the most common symptom for both renal cell and transitional cell cancer is blood in the urine (hematuria), although this occurs in only 40% to 50% of patients. Other possible symptoms include persistent pain in the area between the ribs and the hip not associated with an injury, a mass in the area of the kidneys, high blood pressure, rapid and unexplained weight loss, persistent feeling of fatigue, fever not caused by a cold or flu, swelling of the legs and ankles, anemia, fatigue, and intermittent fever. One third of all patients show evidence that the tumor has spread (metastasized) at the time of diagnosis. Many kidney (renal) tumors are found incidentally on x-rays or ultrasound examinations performed for reasons that do not relate to the tumor or any of its potential symptoms. Other screening tools commonly used include complete blood count (CBC) and sequential multiple analysis (SMA-12), particularly liver chemistry tests, excretory urography, and arteriography.
More than 95% of kidney tumors are adenocarcinomas, or also referred to as hypemephroma, renal cell carcinoma, clear cell cancer, or Grawitz's tumor. These tumors locally infiltrate the capsule and are highly angioinvasive, i.e., spreading to the renal vein and vena cava. Oftentimes, these tumors result in widespread hematogenous and lymphatic metastases, especially to the lung, liver, nodes, and bone.
The staging of kidney cancer is based on the revised criteria of TNM staging by the American Joint Committee for Cancer (AJCC) published in 1988. Staging is the process of describing the extent to which cancer has spread from the site of its origin. It is used to assess a patient's prognosis and to determine the choice of therapy. The stage of a cancer is determined by the size and location in the body of the primary tumor, and whether it has spread to other areas of the body. Staging involves using the letters T, N and M to assess tumors by the size of the primary tumor (T); the degree to which regional lymph nodes (N) are involved; and the absence or presence of distant metastases (M)—cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes. Each of these categories is further classified with a number 1 through 4 to give the total stage. Once the T, N and M are determined, a “stage” of I, II, III or IV is assigned. Stage I cancers are small, localized and usually curable. Stage II and III cancers typically are locally advanced and/or have spread to local lymph nodes. Stage IV cancers usually are metastatic (have spread to distant parts of the body) and generally are considered inoperable.
Kidney cancer can be treated with surgery, radiation therapy, chemotherapy, surveillance, adjuvant (additional), or a combination of these treatments. Treatment of kidney cancer depends on the type of cancer, the stage, the size and shape of the tumor, the age and general health of the patient.
Surgery is the most common treatment for renal cell carcinoma, although it may not be appropriate for every patient with this type of tumor. It is difficult to remove the entire tumor without removing the entire affected kidney (nephrectomy), although this may be attempted in specific situations. Surgical removal of the primary tumor is usually recommended when the tumor remains contained within the kidney itself. It also may be used when the tumor extends to the nearby blood vessels or the lymph nodes in the region of the primary tumor (called local or regional lymph nodes). The goal of surgery under these circumstances is to cure the disease. However, if the tumor has metastasized, the goal of surgery is usually palliative (to relieve symptoms), although recent studies have shown that surgical removal of the affected kidney in patients with metastatic renal cell carcinoma, followed by immunotherapy treatment, may prolong survival.
Radiation has not been highly effective as the primary treatment for renal cell carcinoma, though it has been used as palliative therapy for patients with stage IV renal cell carcinoma in an effort to relieve symptoms caused by the tumor. In addition, it has been used on patients without metastasis following surgical removal of the primary tumor within the kidney when the surgical margins are positive for tumor involvement, or if there is known residual tumor following surgery. Radiation is also used to shrink an especially large tumor prior to surgery or to slow the growth of inoperable tumors using either external beam (similar to an x-ray) or brachytherapy (internal radiation delivered with implanted radioactive seeds). It is common for the skin in the treated area to become red, dry, tender, and itchy. Radiation to the kidney and nearby areas may cause nausea, vomiting, diarrhea, or urinary discomfort. It may also cause a decrease in the number of white blood cells, cells that help protect the body against infection.
Many chemotherapeutic drugs have been tried in the past as single agents for the palliation of stomach cancer, but the results were generally disappointing. Nevertheless, the role of chemotherapy in the management of stomach cancer is continually evolving. Oftentimes, chemotherapy with radiation in adjunct to surgery is used. In general, chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease (Ali et al., 2000, Oncology 14(8):1223–30). Unfortunately, the high initial response rates to first line chemotherapy does not appear to translate into a survival benefit (Kohno and Kitahara, 2001, Gan To Kagaku Ryoho 28(4):448–53). Moreover, there are many undesirable side effects associated with chemotherapy such as temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea. Active chemotherapeutic agents include vinblastine, FUDR, hydroxyurea, 5-fluorouracil (5FU), and mitomycin.
The identification of active chemotherapeutic agents against cancers traditionally involved the use of various animal models of cancer. The mouse has been one of the most informative and productive experimental system for studying carcinogenesis (Sills et al., 2001, Toxicol Letters 120:187–198), cancer therapy (Malkinson, 2001, Lung Cancer 32(3):265–279; Hoffman R M., 1999, Invest New Drugs 17(4):343–359), and cancer chemoprevention (Yun, 1999, Annals NY Acad Sci. 889:157–192). Cancer research started with transplanted tumors in animals which provided reproducible and controllable materials for investigation. Pieces of primary animal tumors, cell suspensions made from these tumors, and immortal cell lines established from these tumor cells propagate when transplanted to animals of the same species.
To transplant human cancer to an animal and to prevent its destruction by rejection, the immune system of the animal are compromised. While originally accomplished by irradiation, thymectomy, and application of steroids to eliminate acquired immunity, nude mice that are athymic congenitally have been used as recipients of a variety of human tumors (Rygaard, 1983, in 13th International Cancer Congress Part C, Biology of Cancer (2), pp 37–44, Alan R. Liss, Inc., NY; Fergusson and Smith, 1987, Thorax, 42:753–758). While the athymic nude mouse model provides useful models to study a large number of human tumors in vivo, it does not develop spontaneous metastases and are not suitable for all types of tumors. Next, the severe combined immunodeficient (SCID) mice is developed in which the acquired immune system is completely disabled by a genetic mutation. Human lung cancer was first used to demonstrate the successful engraftment of a human cancer in the SCID mouse model (Reddy S., 1987, Cancer Res. 47(9):2456–2460). Subsequently, the SCID mouse model have been shown to allow disseminated metastatic growths for a number of human tumors, particularly hematologic disorders and malignant melanoma (Mueller and Reisfeld, 1991, Cancer Metastasis Rev. 10(3):193–200; Bankert et al., 2001, Trends Immunol. 22:386–393). With the recent advent of transgenic technology, the mouse genome has become the primary mammalian genetic model for the study of cancer (Resor et al., 2001, Human Molec Genet. 10:669–675).
While surgery, chemotherapeutic agents and radiation are useful in the treatment of kidney cancer, there is a continued need to find better treatment modalities and approaches to manage the disease that are more effective and less toxic, especially when clinical oncologists are giving increased attention to the quality of life of cancer patients. The present invention provides an alternative approach to cancer therapy and management of the disease by using an oral composition comprising yeasts.
2.2 Yeast-Based Compositions
Yeasts and components thereof have been developed to be used as dietary supplement or pharmaceuticals. However, none of the prior methods uses yeast cells which have been cultured in an electromagnetic field to produce a product that has an anti-cancer effect. The following are some examples of prior uses of yeast cells and components thereof:
U.S. Pat. No. 6,197,295 discloses a selenium-enriched dried yeast product which can be used as dietary supplement. The yeast strain Saccharomyces boulardii sequela PY 31 (ATCC 74366) is cultured in the presence of selenium salts and contains 300 to about 6,000 ppm intracellular selenium. Methods for reducing tumor cell growth by administration of the selenium yeast product in combination with chemotherapeutic agents is also disclosed.
U.S. Pat. No. 6,143,731 discloses a dietary additive containing whole β-glucans derived from yeast, which when administered to animals and humans, provide a source of fiber in the diet, a fecal bulking agent, a source of short chain fatty acids, reduce cholesterol and LDL, and raises HDL levels.
U.S. Pat. No. 5,504,079 discloses a method of stimulating an immune response in a subject utilizing modified yeast glucans which have enhanced immunobiologic activity. The modified glucans are prepared from the cell wall of Saccharomyces yeasts, and can be administered in a variety of routes including, for example, the oral, intravenous, subcutaneous, topical, and intranasal route.
U.S. Pat. No. 4,348,483 discloses a process for preparing a chromium yeast product which has a high intracellular chromium content. The process comprises allowing the yeast cells to absorb chromium under a controlled acidic pH and, thereafter inducing the yeast cells to grow by adding nutrients. The yeast cells are dried and used as a dietary supplement.
Citation of documents herein is not intended as an admission that any of the documents cited herein is pertinent prior art, or an admission that the cited documents are considered material to the patentability of the claims of the present application. All statements as to the date or representations as to the contents of these documents are based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.